Abstract

Selenium, an essential biological trace element, has been shown to reduce and prevent the incidence of cancer. Our previous studies have shown that selenite is involved in the chemoprevention of cancer and induction of apoptosis of cancer cells. In this study, we demonstrate that selenite also inhibits the invasion of tumor cells. Cancer cell invasion requires coordinated processes, such as changes in cell-cell and cell-matrix adhesion, degradation of the extracellular matrix, and cell migration. We found that selenite inhibited invasion of HT1080 human fibrosarcoma cells. Adhesion of HT1080 cells to the collagen matrix was also inhibited by treatment with selenite, but cell-cell interaction and cell motility were not affected by selenite. Moreover, selenite reduced expression of matrix metalloproteinase-2 and -9 and urokinase-type plasminogen activator, which are involved in matrix degradation, but increased a tissue inhibitor of metalloproteinase-1. This inhibitory effect of selenite on the protease expressions was mediated by the suppression of transcription factors, NF-kappaB and AP-1. However, selenate showed no remarkable effect on all the steps of cancer cell invasion.

Highlights

  • Metastasis is the major cause of death among cancer patients

  • Extracellular matrix breakdown is vital to cellular invasion, indicating that matrix-degrading proteinases are essential for tumor cell metastasis

  • We demonstrated here that attachment of HT1080 cells to the type I and IV collagen was significantly decreased after 6 h of pretreatment with 2 ␮M selenite and further dramatically decreased with 3 ␮M

Read more

Summary

EXPERIMENTAL PROCEDURES

Cell Culture and Materials—HT1080 (fibrosarcoma), 293 (embryonic kidney), and MDA-MB-231 (breast adenocarcinoma) cells were grown in DMEM supplemented with 10 mM HEPES, 50 mg/liter gentamicin (Life Technologies, Inc.), and 10% heat-inactivated fetal bovine serum. T98G (glioblastoma) and NUGC-3 (gastric adenocarcinoma) cells were grown in RPMI 1640 supplemented with 10 mM HEPES, 50 mg/liter gentamicin, and 10% heat-inactivated fetal bovine serum. Human type I and IV collagens, bovine serum albumin, gelatin, sodium selenite, sodium selenate, plasminogen, fibrinogen, and thrombin were purchased from Sigma. Anti-MMP-9, anti-TIMP-1, anti-uPA, and anti-uPA inhibitor-1 (uPAI-1) were obtained from Chemicon International, Inc

Selenite Inhibits Tumor Cell Invasion
RESULTS
DISCUSSION
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call